HIV Salvage Therapy (Holden Young - Roseman University of Health Sciences)

1. HIV Salvage Therapy
Holden Young, PharmD Candidate 2021 and Leah Presbitero, PharmD Candidate 2022
HIV Background HIV Salvage Therapy Treatment Options for Multidrug-Resistance (MDR) without
Fully Active Antiretroviral Regimens
HIV is a RNA virus that attacks the body’s
immune system, which allows the virus to
replicate, resulting in a lower CD4 count
Risk Factors:
 Inconsistent condom use
 Injection drug use (IDU)
 Men who have sex with men (MSM)
 Commercial sex worker
 Untreated STIs
Transmission: Contact with bodily fluids (blood,
anal secretions, and vaginal secretions) through:
 Sexual intercourse
 IV drug use
 Vertical transmission
Diagnostic Tests:
 4th
generation HIV antigen/antibody test
 Nucleic Acid Test (NAT)
Mainstay treatment of HIV consists of a backbone of 2 NRTI’s and either a protease
inhibitor or integrase inhibitor
HIV Salvage Therapy: Given when standard treatment results in virologic failure
and/or fails to achieve a viral load < 200 copies/mL after 6 months
Fostemsavir (Rukobia) Ibalizumab (Trogarzo)
MOA
Blocks the conformational
change required for
attachment of the virus to the
CD4 cell surface receptors
Recombinant humanized
monoclonal antibody that
causes a conformational
change that blocks the
interaction of gp120 and HIV
Goal of Salvage Therapy: decrease viral load to undetectable
(< 50 copies/mL), but if not attainable, to the lowest level possible
 Regimens for salvage therapy should include 2-3 fully active agents that are
uncompromised on the patients ART history, past and current drug resistance
 Re-check viral load at 2-8 weeks, then every 4-8 weeks until suppressed
 Once suppressed, monitor viral load every 3-6 months
Dose 1 ER tablet (600 mg) by mouth
twice daily + food
IV loading dose of 2 g, then
IV maintenance dose of 800
mg every 2 weeks
Warnings IRIS
QTC prolongation
IRIS
Virologic Failure
Virologic Failure: > 2 tried and failed regimens and/or evidence of resistance to at
least one drug in each of the major classes
Clinical Trial
BRIGHTE
Evaluated the safety and
efficacy of adding fostemsavir
to an optimized background
regimen in HTE patients living
with MDR HIV-1 with limited
therapy options
By day 8, there was an
average decrease of 0.79 log10
copies/mL in HIV-1 RNA in
patients who received
fostemsavir with an optimized
background regimen
The most common side effects
were nausea and diarrhea
TMB-301
Evaluated the safety and
efficacy of adding ibalizumab
to an optimized background
regimen in treatment-
experienced patients living
with MDR HIV-1
By day 14, 83% of patients
who received ibalizumab with
an optimized background
regimen had a decrease of at
least 0.5 log10 copies/mL
The most common side effects
were diarrhea, fatigue, rash,
dizziness, nausea, and pyrexia
Causes of Virologic Failure:
 Resistance due to prior treatment
failure, innate resistance
 Adherence due to cost, side
effects, pill burden, unstable
housing, missed appointments
To Manage Virologic Failure, review:
 HIV RNA
 CD4 Count
 ART history
 Past and current ART resistances
 Potential drug and food interactions
A CD4 count < 200 copies/mL is clinically
defined as AIDS
Due to a diminished immune system, those living
with AIDS are at a higher risk for experiencing
opportunistic infections such as Mycobacterium
Avium Complex (MAC), Pneumocystis
Pneumonia (PJP), and Toxoplasmosis
Options for treatment regimens have been
immensely limited in heavily treatment
experienced (HTE) patients living with HIV
Resistance tests should be completed at the same time of the failing regimen or
within 4 weeks of treatment discontinuation
(Specific mutations may not be detected if testing occurs > 4 weeks)
Non-Pharmacological ways to avoid Resistance
 Monitor Adherence: self- supporting, pharmacy refill checks, reminder devices
 Simplified regimens: once-daily regimens, fixed-dose combinations
 Specialized counseling: peer support groups
 Food supplementation packages: reduce side effects to improve adherence Approval Date July 2, 2020 March 6, 2018
References
1. HIV. Centers for Disease Control and Prevention. 2021, June 1. Available from: https://www.cdc.gov/hiv/basics/whatishiv.html
2. Salvage Therapy. The AIDS InfoNet. 2018, April 30. Available from: http://www.aidsinfonet.org/fact_sheets/view/408.
3. Collins, Simon. Salvage Therapy. BETA. Winter 2003;15(4):17-28. PMID: 12691034
4. Third line anti-HIV therapy options. Proj Inf Perspect. 2004;(37):19-21. PMID: 15119286
5. Fostemsavir. In: LexiDrugs. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc. Updated June 13, 2021.
6. Ibalizumab. In: LexiDrugs. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc. Updated May 3, 2021.